The ability to introduce nucleic acid into cells is the cornerstone of many molecular biology techniques and their pharmaceutical applications. Many different delivery systems have been developed to introduce exogenous DNA into cells. These include viruses, liposomes, electroporation, cell fusion, microinjection and salt precipitation. (See, e.g., Sambrook et al., Molecular Cloning, a Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.) Although virus proteins and particles can provide efficient means of introducing exogenous DNA into target cells, problems associated with immunogenicity and potential infection have led to the production of synthetic delivery vehicles, such as cationic liposomes. Although many synthetic delivery systems may involve nonspecific cellular uptake, a variety of cell-specific delivery systems are also available.
Synthetic delivery vehicles for introduction of heterologous DNA into specific cells are architecturally complicated and often unstable under various preparatory and/or storage conditions. Not only must the DNA be maintained in a condition that ensures its structural integrity and functionality, the delivery vehicle itself, if attached to a ligand, should maintain the capability of being recognized and internalized by the target cell. It is often the case that a mechanism capable of achieving one of these goals has a negative effect on the other. For example, polycation-nucleic acid condensates in the form of compact particles show great promise as gene delivery vehicles. However, the stability of such condensates in the liquid and frozen state is limited due to their propensity to aggregate and fall out of solution.
Therefore, there exists a need in the art for nucleic acid molecule compositions which maintain their stability under a variety of different conditions that have been shown to destabilize various prior compositions. The present invention fulfills this need, while further providing other related advantages.